The immunosuppressant drug, cyclosporine-A (CS-A), is the drug of choice in organ transplantation. It is also employed in the treatment of psoriasis, systemic lupus erythematosis, type I diabetes mellitus, rheumatoid arthritis and multiple sclerosis. Connective tissue related side effects, such as cardiac and renal fibrosis, and enlargement and overgrowth of the gingiva have been reported. The incidence of CS-A induced gingival overgrowth may be as high as 50-80% in humans. The histopathogenesis of the lesion has not been reported. An animal model is sorely needed, and the Beagle may be appropriate. The gingiva of Beagles undergoing daily CS-A therapy will be evaluated for gross clinical and histological (light microscopy) changes during 7 months of treatment, thus providing qualitative and quantitative data concerning cellular, matrix and fibrous components of the redundant tissue. The proposed research will provide important quantitative information on lesion severity and rapidity of onset and posttherapeutic regression as well as provide histomorphometric data of the lesion. The gingival changes will also be evaluated during a two month period following cessation of drug therapy to obtain information on what occurs within the tissue after CS-A treatment is terminated. The cellular and fibrous changes observed in the gingiva may also be present during the development of the fibrotic lesions found in the kidney and heart. Therefore, results obtained by studying CS-A induced gingival overgrowth may have an effect in determining the cellular changes in the CS-A induced fibrosis in other tissue. The study may also provide information on how the changes in the connective tissue components that occur during CS-A treatment relate to similar appearing gingival lesions induced by other drugs, such as phenytoin and nifedipine.